Beta-adreneric receptor antagonists (“beta blockers”) represent a broad class of agents employed in the treatment of individuals suffering from a variety of disorders. In the treatment of an individual suffering from hypertension, for example, administration of a beta blocker may lower blood pressure. In addition, individuals suffering from cardiac arrhythmias often benefit from the administration of a beta blocker. Other applications in which beta blockers have been used include the treatment of individuals suffering from migraine, congestive heart failure, angina, anxiety and depression. As a class, beta blockers represent an important and widely used tool in pharmacotherapy.
Although beta blockers serve an important role in treating patients, their use is sometimes associated with (among other things) extensive metabolism in the liver as well as certain CNS side effects. Although some beta blockers (such as pindolol, sotalol and carteolol) have no significant first-pass effect, the reduction of CNS side effects from even these beta blockers would enhance their desirability as therapeutic drugs.
One approach for avoiding the problems associated with extensive first pass metabolism is to administer the drug via intravenous administration. Indeed, when propranolol is administered by the intravenous route, much smaller doses are required to achieve a therapeutic effect than when it is given orally. Intravenous administration, however, requires the use of trained clinical personnel, which may be inconvenient or impractical. In such a case, an orally administrable dosage form of a beta blocker not prone to extensive first pass metabolism would be preferred.
Many beta blockers exert CNS effects as these molecules often penetrate the blood-brain barrier. For example, administration of beta blockers has been associated with dizziness, peripheral neuropathy, paresthesias, sleep disturbances and seizures. As a consequence, pharmacotherapy with beta blockers would be improved if these and/or other side effects associated with their use could be decreased.
The present invention seeks to address these and other needs in the art.